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Hypoxia‐inducible factor (HIF) plays a critical role in the mechanisms that allow cells to adapt to various oxygen levels in the environment. Specifically, HIF‐1⍺ has shown to be widely involved in cellular repair, survival, and energy metabolism. HIF‐1⍺ has also been found in increased levels in cancer cells, highlighting the importance of balance in the hypoxic response. Promoting HIF‐1⍺ activity as a potential therapy for degenerative diseases and inhibiting HIF‐1⍺ as a therapy for pathologies with overactive cell proliferation are actively being explored. Digoxin and metformin, HIF‐1⍺ inhibitors, and deferoxamine and ⍺‐ketoglutarate analogues, HIF‐1⍺ activators, are being studied for application in age‐related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, these same medications have retinal toxicities that must be assessed before implementation of therapeutic care. Herein, we highlight the duality of therapeutic and toxic potential of HIF‐1⍺ that must be carefully assessed prior to its clinical application in retinal disorders. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development. [ABSTRACT FROM AUTHOR]

Purpose: To report a novel case of Paracentral Acute Middle Maculopathy (PAMM) Secondary to Retinal Artery Macroaneurysm. Methods: A case report. Results: A 72‐year‐old lady presented with three‐month history of sudden onset left paracentral scotoma. Her medical history include hypertension and hyperlipidemia. Visual acuity was 6/7.5 and 6/45 in the right and left eye respectively. Anterior segment examination and intraocular pressures were unremarkable. A ruptured retinal arterial macroaneurysm (RAM) was seen along the second‐order artery along the inferotemporal arcade with a small area of deep‐retinal whitening along the distal branches of the artery. Corresponding optical coherence tomography showed a round superficial retinal hyperreflective lesion consistent with RAM and hyperreflective band involving the outer plexiform layer (OPL), inner nuclear layer (INL) and inner plexiform layer (IPL) consistent with PAMM. Confocal scanning laser ophthalmoscopy video fluorescein angiogram (FA) demonstrated a ruptured and hemorrhagic RAM with significantly delayed distal filling of the artery, with resultant PAMM in an area supplied by the tributary arterioles of the affected artery. Conclusions: Oxygen consumption is highest at the metabolically active middle retinal layer. The inner and middle retinal layers are supplied by the superficial capillary plexus in the ganglion cell layer, intermediate capillary plexus (ICP) in the INL‐IPL boundary and deep capillary plexus (DCP) in the INL‐OPL boundary. Rupture and partial thrombosis of the RAM resulted in mechanical narrowing of the vessel lumen and severe flow limitation, which was further exacerbated by her history of hypertension and hyperlipidemia. This was consistent with the FA findings of delayed filling in the distal parts of the artery. Flow limitation results in decreased blood supply to the retinal capillary plexuses, further decreasing perfusion pressure, causing most disruption to the delicately balanced ICP and DCP blood supply of the middle retinal layer. Middle retinal infarction occurs most readily and presents as PAMM in our patient. In conclusion, we described a novel case of PAMM secondary to a ruptured and partially thrombosed RAM which clearly elucidates the anatomy and physiology of retinal capillary plexuses. [ABSTRACT FROM AUTHOR]